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Biomedical subjects

H Brown

Publications and source records attributed to H Brown.

At least 55 records · Page 3Linked to original sources
PubMed2000

Peritubular capillaries in chronic renal allograft rejection: a quantitative ultrastructural study.

Peritubular capillaries (PCs) with a circumferentially multilayered basement membrane have been suggested as an ultrastructural indicator of chronic renal allograft rejection (CR). The authors validated this lesion as a marker for CR, by analyzing its quantitative features, specificity, and sensitivity in 169 renal biopsy specimens. The mean number of circumferential layers (PCcirc) and the incidences of the grades (mild: 2 to 4, moderate: 5 to 6, severe: 7 or more layers) were investigated in biopsy specimens involving CR (CR(Bx), n = 46), acute rejection (n = 11), normal kidneys (n = 20), psoriatics treated with cyclosporine (n = 13), renal transplants with chronic cyclosporine toxicity (n = 12), native kidney diseases (NKD, n = 56), and transplant nephrectomies attributable to CR (Cr(nephr), n = 11). CR was diagnosed with regard to the clinical features and the presence of intimal fibrosis in 41 biopsy specimens or transplant glomerulopathy in 35 biopsy specimens (cg; identified only by electron microscopy in 10 cases). NKD included chronic glomerulonephritis, chronic tubulointerstitial nephritis, benign nephrosclerosis, thrombotic microangiopathy, diabetic nephropathy, and renal disease in elderly patients (median age, 72 years). All PCs around glomeruli were sampled (median, 14 profiles per case). PCs with a moderate/ severe lesion appeared as serrated profiles with a thick, ribbon-like basement membrane layer in semithin plastic sections. The numbers of circumferentially multilayered PCs were significantly characteristic of CR (PCcirc in CR(Bx): 2.87+/-1.83 SD; range, 0 to 7.36; P < .001 v other groups). A severe lesion occurred exclusively in CR (in 12% of the PCs in CR(Bx), and in 38% in CRnephr). A moderate lesion was observed in 0.6% of the PCs in NKD, 16% in CR(Bx), and 21% in CRnephr. Three or more PCs with a moderate lesion were encountered only in CR. A mild lesion was not suggestive of CR at all. In CR(Bx), 27 cases showed a severe lesion or 3 or more PCs with a moderate lesion (cpc; sensitivity: 59%). Four of the 27 cases lacked cg. The cumulative incidence of cpc and cg was 85%. In transplants with cyclosporine toxicity, the presence of cpc verified the coexistence of CR in 7 specimens. In conclusion, cpc is a specific marker of CR. The incidence of cpc increases as CR progresses. The lesion may be caused by a low-grade rejection injury to the PCs. Careful analysis of semithin sections promotes the better sampling of cpc. An ultrastructural demonstration of cpc and cg defines CR more precisely than does light microscopic evaluation per se.

Adolescent↗
PubMed2000

Incremental cost-effectiveness of laser therapy for choroidal neovascularization associated with histoplasmosis.

PURPOSE: Laser photocoagulation has been shown in a large clinical trial to be efficacious in reducing the degree of vision loss occurring secondary to choroidal neovascularization (CNV) associated with ocular histoplasmosis. Nevertheless, data are lacking concerning the impact of the therapy on quality of life and its value to stakeholders in health care. Recently, information concerning the utility value of visual states has become available. Accordingly, the authors undertook to ascertain the cost-effectiveness of laser photocoagulation for the treatment of extrafoveal CNV occurring in eyes with ocular histoplasmosis. METHODS: Design--A computer simulation, econometric model is presented to evaluate the incremental cost-effectiveness of laser photocoagulation therapy, as compared with the natural course of the disease, for the treatment of patients with extrafoveal CNV associated with ocular histoplasmosis. The model applies long-term visual data from previous clinical trials, utility analysis (which reflects patient perceptions of quality of life), decision analysis with Markov modeling, and present value analysis with discounting to account for the time value of money. Outcome measure--Cost per quality-adjusted life-year gained from treatment. RESULTS: Laser photocoagulation therapy for extrafoveal CNV associated with ocular histoplasmosis costs $4167 1999 US dollars (at a 3% discount rate) for each quality-adjusted life-year gained from treatment. Sensitivity analysis shows that changing the discount rate substantially alters the cost-effectiveness, with a value of $1339 at a 0% discount rate and $56,250 at a 10% discount rate. CONCLUSIONS: Compared with therapeutic modalities for other disease entities, laser therapy for the treatment of extrafoveal CNV associated with ocular histoplasmosis appears to be a cost-effective treatment from the patient preference-based point of view.

Adult↗
PubMed2000

Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis.

Synaptotagmin is involved in Ca2+-regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic beta-cell is an example of a Ca2+-dependent secretory process. Previous studies of pancreatic beta-cells were unable to show presence of synaptotagmin I. We now present biochemical and immunohistochemical data showing that synaptotagmin III is present in pancreatic beta-cells as well as in the insulin-secreting cell line HIT-T15 and in rat insulinoma. By subcellular fractionation, we found synaptotagmin III in high-density fractions together with insulin and secretogranin I, indicating colocalization of synaptotagmin III and insulin in secretory granules. We could also show that blockade of synaptotagmin III by a specific antibody inhibited Ca2+-induced changes in beta-cell membrane capacitance, suggesting that synaptotagmin III is part of the functional protein complex regulating beta-cell exocytosis. The synaptotagmin III antibody did not affect the activity of the voltage-gated L-type Ca2+-channel. These findings are compatible with the view that synaptotagmin III, because of its distinct localization in the pancreatic beta-cell, functionally modulates insulin exocytosis. This indicates that synaptotagmin may have a general role in the regulation of exocytosis not only in neuronal cells but also in endocrine cells.

Animals↗
PubMed2000

American Association of Cancer Research - 91st annual meeting.

The goal of the American Association for Cancer Research (AACR) 91st annual meeting was to provide all attendees, regardless of area of scientific interest or professional status, with a better understanding of the latest findings in all areas of cancer research, with the overall aim of aiding the implementation of these findings in the diagnosis, treatment and prevention of cancer. Thus, in addition to almost 5600 posters, poster discussion sessions and minisymposia, a timetable of symposia, educational sessions, workshops and press sessions put the exciting developments revealed at the conference into scientific context for delegates not expert in each field.

Journal Article↗
PubMed2000

Advances in anti-arthritic agents. 24-25 January 2000, London, UK.

This meeting provided an excellent overview of the field of arthritis, although most of the drugs mentioned were designed to treat rheumatoid arthritis. There was an air of excitement surrounding the event because, after a substantial period of dormancy in clinical rheumatology, there are now many promising new treatments emerging, which, it is hoped, will greatly improve the quality of life for numerous arthritis sufferers. Speakers covered topics as diverse as care for sufferers, impact of the disease, status of current treatments, and approaches for the future. The majority of the presentations were drug-oriented; the speaker generally gave a summary of their company's arthritis research program and then followed this with a case study of its lead compound.

Journal Article↗
PubMed1999

Netlines

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Journal Article↗
PubMed1999

Image analysis of gunshot residue on entry wounds. I--The technique and preliminary study.

An automated image analysis (IA) technique has been developed to obtain a measure of the amount (i.e. number and area) of gunshot residue (GSR) particles within and around a gunshot wound. Sample preparation and IA procedures were standardised to improve the reproducibility of the IA measurements of GSR. Measurements of GSR from test firings into goat hide were enhanced by staining the barium and lead components present on the skin sections with Alizarin Red S. The amount of GSR detected on the stained skin sections was compared with backscatter electron micrographs of the same sections. The differences were deemed to be insignificant when the variability in the repeated test firings were taken into consideration. Preliminary results indicated that the decreasing relationship between firing range and the amount of GSR deposited was non-linear, and that for firing ranges of up to 20 cm the amount of GSR deposited from repeated shots fired from the same distance was highly variable.

Animals↗
PubMed1999

Image analysis of gunshot residue on entry wounds. II--A statistical estimation of firing range.

A statistical investigation of the relationship between firing range and the amount and distribution of gunshot residue (GSR), used automated image analysis (IA) to quantify GSR deposit resulting from firings into pig skin, from distances ranging between contact and 45 cm. Overall, for a Ruger .22 semi-automatic rifle using CCI solid point, high velocity ammunition, the total area of GSR deposit on the skin sections decreased in a non-linear fashion with firing range. More specifically there were significant differences in the amount of GSR deposited from shots fired at contact compared with shots fired from distances between 2.5 and 45 cm; and between shots fired from a distance of 20 cm or less, with shots fired at a distance of 30 cm or more. In addition, GSR particles were heavily concentrated in the wound tract only for contact and close range shots at 2.5 cm, while the particle distribution was more uniform between the wound tract and the skin surfaces for shots fired from distances greater than 2.5 cm. Consequently, for future scientific investigations of gunshot fatalities, once standards have been established for the weapon and ammunition type in question, image analysis quantification of GSR deposited in and around the gunshot wound may be capable of providing a reliable, statistical basis for estimating firing range.

Animals↗
PubMed1999

Netlines

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Burkholderia cepacia is resistant to the antimicrobial activity of airway epithelial cells.

There has been much interest recently in the antimicrobial properties of cationic peptides called beta-defensins from epithelial cells. Human beta-defensin (hBD)-1 and -2 have been particularly implicated in cystic fibrosis (CF) patients, where their inhibition by high salt concentrations may explain in part the susceptibility of the CF lung to bacterial infection. In this work, we have employed a simple co-culture system using the 16-HBE human bronchial epithelial cell line to assess growth inhibitory activity against Pseudomonas aeruginosa and Burkholderia cepacia. In medium alone, P. aeruginosa proliferated more than 100,000-fold, whereas in the presence of 16-HBE cells or 16-HBE-conditioned medium, bacterial proliferation was less than 100-fold. Raising the salt concentration of cell-free 16-HBE conditioned medium to approximately 200 mM significantly reduced this growth inhibitory activity. In contrast, there was no evidence of epithelial-derived growth inhibitory activity against two strains of B. cepacia. RT-PCR analysis indicated expression of the hBD-2 mRNA in 16-HBE cells, but not hBD-1. These data demonstrate for the first time that B. cepacia is resistant to epithelial-derived antimicrobial substances and argue against them being important in the defense against this organism in the lung.

Burkholderia cepacia↗
PubMed1999

Evidence of blood-brain barrier dysfunction in human cerebral malaria.

Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome. Adhesion of parasitized red blood cells in the brain microvasculature is mediated by specific receptors on the host endothelium, including intercellular adhesion molecule (ICAM)-1, CD36 and CD31. Leucocyte binding to cerebral endothelial cells in culture induces intracellular signalling via ICAM-1. The hypothesis that parasitized red blood cells binding to receptors on cerebral endothelial cells causes changes in the integrity of the blood-brain barrier was tested. Immunohistochemistry was used to examine the blood-brain barrier in human cerebral malaria, with antibodies to macrophage and endothelial activation markers, intercellular junction proteins, and plasma proteins. The distribution of the cell junction proteins occludin, vinculin and ZO-1 were altered in cerebral malaria cases compared to controls. While fibrinogen was the only plasma protein detected in the perivascular space, there was widespread perivascular macrophage activation, suggesting that these cells had been exposed to plasma proteins. It was concluded that functional changes to the blood-brain barrier occur in cerebral malaria, possibly as a result of the binding of parasitized red blood cells to cerebral endothelial cells. These changes require further examination in vitro.

Adolescent↗
PubMed1999

Cytokine expression in the brain in human cerebral malaria.

Evidence from clinical studies and murine models supports a role for cytokines in the pathogenesis of human cerebral malaria (CM). In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate expression of mRNA for transforming growth factor (TGF)-beta, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha in human postmortem tissue. Immunohistochemistry was used to examine the distribution of cytokine protein. TGF-beta was expressed in normal brain, in CM, and in meningitis and encephalitis. IL-1beta was absent from normal brain but was detected in CM and other cerebral infections. TNF-alpha mRNA was expressed only in CM, although TNF-alpha protein was also seen in meningitis. Cytokine mRNA expression in the brain did not correlate with the density of parasitized erythrocytes detected using RT-PCR for major surface protein-2. This report of RT-PCR on postmortem human tissues infected with CM demonstrates induction of the proinflammatory cytokines TNF-alpha and IL-1beta in the brain.

Antigens, Protozoan↗
PubMed1999

Myositis and malignancy: is there a true association?

There may be an association between polymyositis/dermatomyositis and malignant disease. Cancer occurs in patients with polymyositis/dermatomyositis with a frequency estimated between 2.5% and 29% (relative risk 1.0 to 6.5). We present two such cases, associated with colorectal carcinoma and non-Hodgkin's lymphoma respectively, together with an overview of existing controlled studies in the area.

Adenocarcinoma↗